The present disclosure generally relates to systems and methods employing electrical impedance spectroscopy (EIS) for detecting, characterizing, and monitoring brain injuries and, more particularly, to systems and methods employing the Stochastic Gabor Function (SGF) and dual energy pulses for portably conducting EIS to detect, characterize, and monitor intracranial hemorrhage (ICH), stroke and other forms of traumatic brain injury (TBI). By way of example, one method includes probing using two sequential SGF pulses with two different principal energies, which can more sensitively assess deep brain tissue impedance than current, single pulse paradigms.
Intracranial hemorrhage, stroke, and traumatic brain injury are major public health problems. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are currently the first line modalities for the evaluation of acute brain injury, including hemorrhage and stroke, but are limited in their ambulance, battlefield, and intensive care unit (ICU) availability. On the other hand, Electrical Impedance Spectroscopy (EIS) devices are portable, noninvasive devices that can provide accurate point-of-care detection, rapid triage, and serial monitoring of intracranial pathology—effectively an “EKG for the brain”. For example, such a monitor need not be capable of detailed imaging, but need only alert caregivers of an event in progress, so triage to CT or MRI could be performed.
Traumatic brain injury (TBI) is the leading cause of death among individuals less than 45 years of age, affecting over 7 million people per year (over 10% of whom are hospitalized), and resulting in over 100,000 long-term disabilities and 50,000 pre-hospital admission deaths, costing approximately $50 billion dollars per year. Every 15 seconds someone suffers traumatic brain injury, and in children it accounts for more than all other causes of death combined. Causes of TBI in the United States include motor vehicle accidents (MVA, 45%), falls (20%), sports (15%), and assaults (15%).
Furthermore, with increasing use of improvised explosive devices (IEDs), blast-related concussive injury has become common. Blast waves can cause subdural hematoma, stroke, contusion, white matter hemorrhagic shear injury (“HSI,” typically detectable only with specialized susceptibility weighted MRI sequences), and diffuse axonal injury (“DAI,” similarly only detectable acutely with specialized diffusion weighted MRI sequences). Moreover, even the most advanced current generation MRI pulse sequences, such as diffusion tensor imaging (DTI), magnetization transfer imaging (MT), and MR spectroscopy (MRS), are incapable of detecting the subtle histological changes (for example, micro-edema and cytoarchitectural axonal disruption) associated with acute mild to moderate traumatic brain injury on an individual patient basis.
Prompt evaluation for symptoms of concussion is of high importance. DAI and HSI remain timely and vexing concerns also exist in high school, college, and professional sports (NFL, NHL, boxing). Even when portable CT scanners are available, they remain a limited resource with undependable technical support and few contingency options for equipment breakdown, cannot be used for continuous monitoring, and cannot be deployed by corpsmen in the field for emergent triage of individuals with—otherwise unapparent—subdural and epidural hematomas. A portable EIS device could therefore be of value not only in military and humanitarian assistance missions, but also more broadly in ambulances and intensive care units (ICU's) everywhere.
Stroke affects over 750,000 patients a year in the US, with the annual incidence expected to rise to 1,000,000 by 2050. The majority of strokes are ischemic (approximately 85 percent), caused by thromboembolism; the remainder are hemorrhagic. Both hemorrhagic and ischemic infarction can occur in the setting of trauma. Distinguishing between these is critical, as their prognosis, treatment, and management differ considerably. This distinction is especially important immediately following stroke onset because intracranial hemorrhage is a contraindication to thrombolytic therapy.
“Time is brain” is a well-established principle of stroke care. Early detection of infarction, and the distinction between hemorrhagic and bland ischemic change, is critical for appropriate management. For patients being evaluated for stroke, early diagnosis has a dramatic effect on the effectiveness of treatment. In patients undergoing cardiac catheterization, carotid endarterectomy, and other common endovascular procedures for which stroke is a complication, early detection would allow effective intervention and additional prevention. Further still, early detection of stroke and its complications could result not only in improved clinical outcomes (for example, stroke negatively effects more women per year than does breast cancer), but also in massive savings in rehabilitation costs, lost productivity, and other economic measures. In 2003, an estimated $57.9 billion was spent on stroke care.
When a patient is treated for ischemic stroke using thrombolytic therapy, when monitoring a hemorrhagic stroke in a neurological intensive care unit (NICU), or when monitoring patients undergoing vascular invasive procedures, detection of new or recurrent bleeding or infarct growth is crucial to patient care.
Monitoring by serial clinical neurological exam is difficult or infeasible in intubated, sedated patients, is nonspecific, difficult to quantify, and has relatively poor reproducibility. In the NICU, bedside clinical assessment using the NIH stroke scale score is the cornerstone of periodic monitoring. As expected of any clinical scale, NIHSS has significant limitations. When clinical assessment raises high enough suspicion of worsening of the intracranial lesion, the patient is transported to CT. Transportation of critically ill patients is a huge challenge; moreover, radiation exposure is a growing concern.
As discussed above, both diagnosis and follow-up of intracranial injury typically involve CT or MRI. Both of these modalities require large and expensive machines, even with limited-use “portable” CT. Moreover, CT scanning exposes patients to ionizing radiation. MRI scanning generates strong electromagnetic fields, which make it unsuitable for many patients, and MRI is incompatible with the majority of metallic and electronic hardware. Thus, it is prohibitively expensive and infeasible to continually monitor a patient in an intensive care unit using CT or MRI.
Other options for sensitive real-time monitoring of intracranial injury also have significant shortcomings. For example, invasive intracranial pressure (ICP) monitors, such as “bolts” or ventricular catheters, detect only the most catastrophic changes after ischemic stroke and do not provide information as to whether brain lesions have undergone hemorrhagic transformation. Invasive tools are also unappealing because they require invasive craniotomy and, in addition to the obvious surgical risks, carry risks of infection in this era of super-resistant bacteria (such MRSA and VRE). Even more importantly, they do not provide information regarding spatial localization. Hence, in most ICUs, ICP monitoring is currently limited to only the highest risk patients.
Non-invasive ultrasound technology (that is, transcranial doppler) permits more frequent, intermittent monitoring of a single, somewhat limited parameter: middle cerebral artery velocity. However, such a method is relatively inaccurate, requires a high level of operator expertise, measures only one vessel location at a time, is logistically difficult to implement, and thus impractical.
Near infrared spectroscopy (NIRS, that is, “optical imaging”) and related optoacoustic technology (which analyzes the ultrasound signal directly transmitted from oxy- and deoxy-hemoglobin exposed to oscillating near infrared frequencies of laser light at the skin surface) have some potential as a means of battlefield detection of subdural and epidural hematomas. However, these methods are limited in both their depth of skull penetration (typically on the order of millimeters) and their extent of lateral coverage (a few square centimeters, depending on the probe array size). Moreover and like conventional ultrasound, NIRS and optoacoustic technology require handheld probes for data acquisition. As such, these methods may potentially introduce greater user-dependent variability than other methods.
Electroencephalography (EEG), which relies on non-invasive measurement of voltages produced by neuronal activity across the skull head, in principle could provide continuous monitoring. However, such a method lacks sufficient sensitivity, specificity, speed, and ease of use required for out-of-hospital diagnosis of stroke or TBI. Thus, EEG is typically used primarily for seizure detection and requires highly specialized expertise to administer and interpret.
EIS presents a potential solution for the portable, accurate, point-of-care diagnosis of injured brain. EIS is a relatively inexpensive advancement of “passive” EEG recording, in which minute electrical currents are actively applied across varying electrodes (that is, rather than passively recorded). EIS relies on non-invasive measurement and modeling of the conduction of minute electrical currents through the head, across a spectrum of frequencies. Cerebrospinal fluid (CSF) and in-situ blood, composed mainly of salt water and accounting for much of the brain's volume, have baseline low resistance to current flow. One the other hand, the edema of acute stroke and the blood clot of intracranial hemorrhage cause complex, but measurable, frequency dependent impedance changes, proportional to lesion size, composition, and location.
More specifically, EIS estimates the macroscopic dielectric constants from surface voltage measurements between electrode pairs positioned on the surface of an object (for example, a patient's head) in response to an applied probe current. For example, in one application, an EIS device delivers a small, AC current (generated using a white noise scheme) through a pair of stimulation electrodes. Voltage is recorded across three or more additional sets of bilaterally symmetric electrode pairs, according to a standard 10-20 EEG montage. The transfer function between the white-noise input and the recorded voltages are estimated, and log-log plots of the calculated impedance for each electrode are plotted as a function of the frequencies, which typically range from 100 Hertz (Hz)-100 kilo-Hertz (kHz).
In theory, EIS detects and monitors brain injuries by characterizing these impedance changes. As with MRI, however, impedance changes due to hemorrhage, stroke, and other traumatic brain injuries likely vary with time-post-insult, as the quantity and molecular conformation (and hence electrical properties) of blood clot and edema evolve.
Moreover, unfortunately, spatial localization and histological characterization of these brain injuries with existing EIS devices is limited by the disproportionate surface—as opposed to deep—current flows inherent to existing prototypes. For example, with single frequency EIS systems, one can detect shallow hematomas that create low-impedance anomalies near the skull surface, but detection of deep lesions remains challenging. Given this and the intrinsic lesion variability noted above, further refinement of existing pulse delivery systems is required to optimize the ability of EIS to: (i) reliably distinguish hemorrhagic from non-hemorrhagic injury; (ii) provide accurate anatomic localization; and (iii) sensitively assess lesion size.
From the above, it should be apparent that there is a need for inexpensive, rapid, easy-to-use, rugged, portable, non-invasive systems and methods capable of detecting, monitoring, and characterizing the bleeding or rebleeding associated with intracranial hemorrhage (ICH), the acute (cytotoxic) and subacute (vasogenic) edema associated with stroke, and the other pathological tissue changes associated with traumatic brain injury.